The Food and Drug Administration is reportedly providing guidance and “positive feedback” for a proposed nalmefene product that will last 24 hours, designed for military and first responders to self-administer as a precaution against secondhand fentanyl exposure. TH104 is being developed by Tharimmune, a blockchain-focused digital finance company with a biotech research arm that consists of basically just this product. The company announced November 13 that the FDA will allow the new drug application (NDA) submission without any clinical trials, since it had already completed a TH104 trial as a treatment for chronic itchiness caused by an autoimmune condition.
Nalmefene is an opioid antagonist that since 2023 has been presented as a competitive alternative to the better-known naloxone, mainly because its effects last several hours longer. Contrary to baseless propaganda from law enforcement and misleading research from pharmaceutical companies, nalmefene has no proven overdose-reversal advantage compared to naloxone and has been universally condemned by public health experts for potentially increasing risk of overdose, when administered to people with a physical dependence on opioids.
Promotion of Opvee, the only nalmefene overdose reversal product currently on the market, was recently discontinued amid a settlement with the New York State attorney general’s office, which required manufacturer Indivior to “stop making false statements” about nalmefene having “approvals, characteristics, uses, benefits or qualities that it does not have,” particularly with regard to claims that it performs favorably compared to naloxone.
Tharimmune is developing its nalmefene product for the indication of “Temporary Prophylaxis of Respiratory and/or Nervous System Depression in Military Personnel and Chemical Incident Responders Entering and Area Contaminated with High-Potency Opioids.” TH104 is expected to be a dime-sized sublingual film that sticks to the inside of the cheek, takes effect within 30 minutes and lasts for around 24 hours. Like Indivior, Tharimmune is highlighting its product’s “potential superiority” to naloxone.
Though Tharimmune announced the news November 13, a Securities and Exchange Commission filing indicates that the company first discussed the additional indication with the FDA in March and had received the positive feedback on its Pre-Investigational NDA by July. Tharimmune is planning to file this NDA before it moves forward with the original TH104 indication for chronic itchiness resulting from primary biliary cholangitis, a degenerative autoimmune disease that attacks the liver.
“The buccal film delivery of TH104 is designed as a non-injectable, rapid absorption and convenient to be self-administered, which may be advantageous for first responders who may be wearing full protective gear,” states the November 13 announcement. “Tharimmune is dedicated to advancing TH104 to provide a potentially effective and patient-friendly treatment as an option for those in need, beginning with its critical role in national security.”
In the tradition of several pharmaceutical companies that came before, Tharimmune is going for language choices that could mean TH104 is intended for routine law-enforcement duties or large-scale terrorist attacks, or both.
Despite the awkward commercial failure of Indivior’s nalmefene-based Opvee, the company still has an active contract with the Biomedical Advanced Research and Development Authority (BARDA) to stockpile the product for use by first responders “in accidental or intentional mass casualty situations” caused by extremely hypothetical “biosecurity threats involving synthetic opioids.”
Before that, in 2022 the Department of Defense partnered with Kaleo, Inc. to develop a high-dose naloxone product specifically for use by the military, in the event of equally hypothetical situations where use of “high-potency opioids such as fentanyl analogues as a chemical weapon is suspected.”
Tharimmune did not respond to Filter‘s inquiry about what scenarios TH104 was intended for and whether any federal agencies are interested in purchasing the product.
First responders aren’t the only ones with occupational exposure to fentanyl.
“The foundation for the FDA’s alignment on the submission of an NDA without additional clinical trials rests on the extensive existing data related to the approved active ingredient nalmefene,” Tharimmune states on its website. “This includes a comprehensive understanding of its safety profile, established through years of use in approved products, and evidence of its efficacy for opioid overdose.”
On November 11, two days before Tharimmune’s announcement, the American College of Medical Toxicology (ACMT) and American Academy of Clinical Toxicology (AACT) published a position statement focused on passive opioid exposure among first responders. It warns that nalmefene has “limited data regarding its use in fentanyl overdose” and “should not be considered the first-line agent for opioid reversal until more robust data are available.” In 2023 the ACMT and AACT published a position statement focused on nalmefene specifically, describing why it should not be used in place of naloxone.
The FDA did not respond to Filter‘s request for comment.
The new position statement, which is excellent, systematically debunks the myths that fentanyl overdose can result from passive inhalation (breathing in particles of fentanyl that might be swirling in the air) or absorption through the skin or mucous membranes.
It makes clear that fentanyl-based terrorist attacks are “beyond the scope of this document,” but does state that in “exceptional circumstances where there are drug particles or droplets suspended in the air, an N95 respirator” would suffice. It also states that in the “unlikely event of environmental opioid poisoning due to handling fentanyl (or any opioid), naloxone should be administered” only if someone is actually exhibiting symptoms of opioid overdose.
First responders aren’t the only ones with occupational exposure to fentanyl. Drug sellers, drug users, hospital workers, pharmaceutical researchers, forensics scientists, lab technicians, overdose prevention center staff—none of them ever need “sustained prophylaxis” before they can enter a room with fentanyl in it.
The myth that fentanyl and other “ultrapotent opioids” are evolving to the point that a standard dose of naloxone is no match for them only exists because once you sell the public that problem, the FDA will entertain your (potentially) very lucrative solutions. Half a dozen nalmefene or higher-dose naloxone products have been approved in the past four years. To date, there has never been a single confirmed report of intoxication from passive opioid exposure.
Image (cropped) via United States Department of Justice/YouTube